More than one quarter of US adults are cigarette smokers and the vast majority would like to stop smoking. Among smokers unable to do so on their own, treatments that enable many of these smokers to quit in the short-term have been developed. However, whether stopping on their own or with the help of formal programs, it is clear that more than half of initial successes will return to smoking. This study will examine the problem of tobacco relapse. The primary aim of this study is to test whether, after achieving initial success, the risk of relapse during the next several months can be significantly reduced by maintenance pharmacotherapy. Seven hundred and fifty subjects (50 percent female, 50 percent white, 25 percent African American, 20 percent Hispanic, 5 percent Asian or Other) will be entered initially in an open treatment phase. Roughly 400 of the successes from this open treatment will be randomized in double- blind fashion, in a 2 x 2 factorial design to one of four treatment arms (bupropion or placebo and nicotine gum or placebo gum). The primary efficacy measure will be time to relapse according to treatment condition. Data obtained from this study will be examined further to address three additional aims: 1) to understand the effects on relapse of psychological (e.g., number of cigarettes smoked, nicotine dependence level, major depression history, personality factors, weight gain) and sociodemographic factors (e.g., age, gender, race, socioeconomic status) identifiable either before treatment begins or after initial cessation has occurred: 2 ) to conduct a cost-effectiveness analysis comparing the incremental societal costs and effects (i.e., treatment costs, smoking relapses prevented, lives saved, life-years saved, and quality of life years saved) of the active maintenance treatments compared with no maintenance treatment; and 3) collect and DNA samples for future genetic studies.